In 2013, about 143,000 people in the United States will be diagnosed with colorectal cancer. In that same year, an estimated 50,830 deaths from colorectal cancer will occur in the United States. Colorectal cancer is the fourth most common cancer in men, after skin, prostate, and lung cancer. It is also the fourth most common cancer in women, after skin, breast, and lung cancer. Methods for determining risk of recurrence or prognosis in colorectal cancer patients would be of great benefit for guiding treatment decisions for these patients. Described herein is the generation of an independently significant, multi-marker prognostic method for colorectal cancer. The data demonstrate the potential for multi-marker assays in improving prognostic assessment of colorectal cancer. The methods described herein allow assignment of a subject at the time of diagnosis of colorectal cancer into a high risk for recurrence or a low risk for recurrence group. The methods will assist patients and physicians in determining the need for adjuvant intervention or at least aggressive follow-up surveillance. The goal of the described methods is to improve the overall survival of the high risk patient group without exposing the remaining patients to the risks and costs associated with adjuvant therapy or monitoring for recurrence of disease.